Clinical consequences of carotid artery (CA) plaque rupture include transient ischemic attacks and ischemic stroke. Carotid endarterectomy (CEA), an open surgical procedure, is the standard intervention in patients with advanced CA atherosclerosis. Patient-specific biomechanical analysis can aid in risk stratification of patients with known CA atherosclerosis, to identify those asymptomatic patients at higher risk of stroke who could benefit from more aggressive medical and/or surgical treatment. However, a shortage of material property data limits clinical application of recent advances in patient-specific biomechanical simulations, particularly material properties specific to clinically well-defined patient subsets. Despite evidence that women with moderate, symptomatic carotid artery stenosis (CAS) derive less benefit from CEA than men in terms of event-free survival after surgery, gender-specific differences in material properties of human CA plaques have not been measured. In addition, to move patient-specific biomechanical analysis forward as a predictive clinical tool, quantitative measurements of changes in fibrous cap strength with time in response to cyclical loading (material fatigue behavior) are essential. Using CEA specimens and clinical imaging data (duplex ultrasound and CTA), we propose to examine gender differences in fibrous cap material properties and the effect of material fatigue on these properties over time. We propose the following Specific Aims: 1) To measure rupture resistance of fibrous caps in male vs. female CEA specimens, and to determine whether gender independently associates with rupture resistance; and 2) To measure the material fatigue behavior of fibrous cap specimens classified by gender and age, and to determine how biophysical properties of carotid plaque fibrous caps evolve with time due to material fatigue, as quantified by maximum circumferential stress and number of loading cycles. Resistance to rupture will be measured as ultimate tensile strength, fracture toughness, and fibrous cap adhesion strength. We expect data from this pilot study to support future, patient-specific computational simulations and accelerate development of improved risk stratification algorithms for patients with moderate, asymptomatic CAS, by identifying gender-specific mechanical stress thresholds to define high risk plaques in males and females. We also expect that quantitation of fibrous cap material fatigue behavior will enable us to introduce time-dependence into the predictive algorithm for plaque failure. These efforts will contribute to the growing trend in precision medicine, using patient-specific data for improved risk stratification and selection of individualized treatment plans.